Search

Despite recent advances in cancer therapeutics, pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease with a 5-year overall survival of only 10%. Since either at or within a few months of diagnosis, most patients with PDAC will present with metastatic disease, a more individualized approach to select patients who may benefit from more aggressive therapy has been suggested. Although studies have reported improved survival in PDAC and isolated pulmonary metastasis (ISP) compared to extrapulmonary metastases, such findings remain controversial. Furthermore, the added benefit of pulmonary metastasectomy and other lung-directed therapies remains unclear. In this review, we discuss the metastatic pattern of PDAC, evaluate the available evidence in the literature for improved survival in PDAC and ISP, evaluate the evidence for the added benefit of pulmonary metastasectomy and other lung-directed therapies, identify prognostic factors for survival, discuss the biological basis for the reported improved survival and identify areas for further research.

Background. Graft-versus-host disease (GVHD) is a potentially fatal complication of allogeneic hematopoietic stem cell transplant. The mainstay of treatment is corticosteroids, which are ineffective in 30–50% of cases. Steroid-refractory GVHD (SR-GVHD) confers a poor prognosis, with high mortality rates despite appropriate therapy. While there is no reliable treatment for SR-GVHD, a variety of novel therapeutic options are slowly emerging and have yet to be examined simultaneously. Objectives. This review evaluates the potential of novel therapeutic options, as well as their efficacy and safety, for the treatment of SR-GVHD. Study Design. The literature search was conducted in PubMed, Cochrane, and Embase, employing MeSH terms and keywords. The studies had to be prospective phases 1, 2, or 3. We excluded retrospective and nonoriginal studies. Results. While the only approved drug for acute GVHD is ruxolitinib with an impressive overall response rate of 73.2% and a complete response of 56.3%, several monoclonal antibodies and other agents are currently under investigation, offering promising results. These include anti-CD2, anti-CD147, IL-2 antagonist, a mixture of anti-CD3 and anti-CD7 antibodies, anti-CD25, monoclonal antibody to a4b7 on T-cells, anti-CD26, pentostatin, sirolimus, denileukin diftitox, infliximab, itacitinib, and alpha-1 antitripsin. However, the toxicities associated with these novel drugs need further investigation. For chronic GVHD, approved options include ruxolitinib with an ORR of up to 62%, ibrutinib with an ORR of up to 77%, and belumosudil with an ORR of up to 77%. Meanwhile, emerging treatments include tyrosine kinase inhibitors such as nilotinib, rituximab, and low-dose IL-2, as well as axatilimab and pomalidomide. Conclusion. While their efficacy needs to be better evaluated through large-scale, multicenter, randomized clinical trials, these novel agents show potential and could provide a better alternative for SR-GVHD treatment in the future.

According to one estimate, zinc supplementation is widely used in the USA by almost 37% of the elderly population above age 71. Zinc has perceived benefits of immune system enhancement without realizing the harmful effects when used in excess. One of its under-recognized side effects is hypocupremia or copper deficiency due to excessive gastrointestinal losses as excessive zinc in the gut competes with copper for absorption. If severe, hypocupremia can cause hematologic changes (anemia, leukopenia/neutropenia, thrombocytopenia, and pancytopenia) with and without neurological deficits. Since zinc-induced hypocupremia is an overlooked entity, there is a lag of 12 months between the onset of symptoms and diagnosis. Most patients usually undergo a series of costly and sometimes invasive tests such as bone marrow biopsies during this lag time. Once diagnosed, the treatment is as simple as discontinuation of zinc and oral copper supplements. Here, we present a case report of zinc-induced hypocupremia and pancytopenia in an 81-year-old lady who was taking zinc supplements for macular degeneration. The patient presented with leukopenia with neutropenia, thrombocytopenia, and moderate anemia. This case report aims to educate clinicians since this is an easily missed entity and likely more prevalent than known due to widely used zinc supplementation.

Abstract The most common etiology of malignant brain tumors is metastatic lesions. They usually present as multiple lesions at the gray‐white matter junction. However, they can unconventionally present as a single space‐occupying lesion mimicking meningioma.

Abstract Hypocupremia due to zinc products can cause sideroblastic anemia and neutropenia and mimics other serious hematological disorders. Early consideration of the copper deficiency and a thorough clinical history can prevent unnecessary interventions.

Abstract Secondary immune‐related hemophagocytic lymphohistiocytosis is a rare but life‐threatening complication of immune checkpoint inhibitors. HLH‐2004 and HLH‐1994 guidelines originally developed for primary HLH are the only available guidelines. It has proven to have a good prognosis if diagnosed promptly with discontinuation of immunotherapy and treated with corticosteroid monotherapy.

Belantamab mafodotin (belamaf), an antibody-drug conjugate approved for the treatment of relapsed and refractory multiple myeloma (RRMM), is an anti B-cell maturation antigen (BCMA) agent. DREAMM-1, a first in-human trial of belamaf, reported several ocular toxicities requiring dose adjustments, dose delays and treatment discontinuations. In DREAMM-1, 53% of patients in part-1 and 63% of patients in part-2 had ocular toxicity. Similarly, 73% of patients in DREAMM-2 had keratopathy (71% in 2.5 mg/kg versus 75% in 3.4 mg/kg) with the most common symptoms being blurred vision and dry eyes. Ocular toxicity of belamaf is attributed to microtubule-disrupting monomethylauristatin-F (MMAF), a cytotoxic payload of the drug that causes an off-target damage to the corneal epithelial cells. Ocular adverse events (AEs) of belamaf are more frequent at higher doses compared with lower doses. Higher belamaf dose, history of dry eyes and soluble BCMA are associated with increased risk of corneal toxicity. Absence of ocular symptoms does not exclude the possibility of belamaf-induced ocular toxicity, so patients need slit lamp and Snellen visual acuity testing to detect microcytic-like epithelial changes and visual decline. Corticosteroid eyes drops for 4-7 days prior to belamaf dose do not prevent ocular AEs and may cause steroid-related AEs instead. Keratopathy and Visual Acuity scale (KVA) is recommended to document the severity of belamaf-induced ocular toxicity and make treatment adjustments. Management of toxicity includes dosage modifications, treatment interruption or discontinuations and preservative-free artificial tears along with close ophthalmology and hematology-oncology follow-ups.

Background: We report post-coronary artery bypass outcomes and factors affecting the outcomes from the Genesee County, MI, where the population is distinctly characterized by a higher prevalence of renal failure (RF), diabetes, obesity and smoking than the national average. Methods: We performed a retrospective cohort study on 1133 patients undergoing isolated CABG at our hospital from June 2012 to July 2017. Primary outcome was the association between preoperative hemoglobin A1c (HbA1c) and all-cause postoperative mortality after CABG, secondary outcomes included the association between HbA1c and a composite of postoperative infections including sternal-wound infections, leg harvest-site infections, pneumonia or sepsis. Logistic Regression analyses were also performed. Results: There was no difference in the mortality rate (OR 1.0, 95% CI 0.4–2.3) and composite of all infections (OR 1.0, 95% CI 0.7–1.6) between the controlled (HbA1c ≤7%) and uncontrolled (HbA1c >7%) groups. However, RF (OR 5.9, 95% CI 1.5–22.9), smoking (OR 3.7, 95% CI 1.3–11.2) and ejection fraction

Pancreatic cancer is one of the most aggressive malignancies of the digestive tract and carries a poor prognosis. The majority of patients have advanced disease at the time of diagnosis. Surgical resection offers the only curative treatment, but only a small proportion of patients can undergo surgical resection. Radiofrequency ablation (RFA) is a well-known modality in the management of solid organ tumors, however, its utility in the management of pancreatic cancer is under investigation. Since the past decade, there is increasing use of RFA as it provides a feasible palliation treatment in the management of unresectable pancreatic cancer. RFA causes tumor cytoreduction through multiple mechanisms such as coagulative necrosis, protein denaturation, and activation of anticancer immunity. The safety profile of RFA is controversial because of the high risk for complications, however, small prospective and retrospective studies have shown promising results in its applicability for palliative management of unresectable pancreatic malignancies. In this review, we discuss different approaches of RFA, their indications, technical accessibility, safety, and major complications in the management of unresectable pancreatic cancer.

Multiple myeloma (MM) is characterized by malignant proliferation of malignant plasma cells; it is the second most common hematological malignancy associated with significant morbidity. Genetic intricacy, instability, and diverse clinical presentations remain a barrier to cure. The treatment of MM is modernized with the introduction of newer therapeutics agents, i.e., target-specific monoclonal antibodies. The currently available literature lacks the benefits of newer targeted therapy being developed with an aim to reduce side effects and increase effectiveness, compared to conventional chemotherapy regimens. This article aims to review literature about the current available monoclonal antibodies, antibody-drug conjugates, and bispecific antibodies for the treatment of MM.

Inflammatory fibroid polyps (IFPs) are rare mesenchymal lesions that can arise throughout the gastrointestinal tract. These tumors represent less than 0.1% of all gastric polypoid lesions and are frequently found incidentally on endoscopic evaluation. While presenting symptoms depend on the location of the tumor, gastric polyps commonly present with epigastric pain and early satiety. We hereby delineate the case of a middle-aged female who presented with chronic iron deficiency anemia and a positive fecal occult blood test. She underwent an upper endoscopy, which revealed an actively oozing umbilicated lesion in the gastric antrum. Endoscopic ultrasound divulged the submucosal origin of the lesion. It was subsequently excised using endoscopic mucosal resection. Pathologic examination of the resected specimen confirmed the diagnosis of gastric IFP. Furthermore, we conducted a systematic literature search of the MEDLINE database centered on gastric IFPs from January 2000 till March 2020. The data on patient demographics, clinical features, endoscopic findings, lesion site and size, and treatment approaches were collected and analyzed. This article illustrates the overarching need for clinicians to be vigilant of gastric IFPs presenting with initial clinical symptoms suggestive of occult upper gastrointestinal bleeding. Prompt diagnosis and management of gastric IFPs carry paramount importance to combat chronic unexplained iron deficiency anemia following occult bleeding in such patients. A concoction of endoscopy, biopsy, and immunohistochemical examination can be employed toward their prompt detection. Although gastric IFPs have conventionally been treated with surgery, endoscopic resection is now emerging as a safe and efficient therapeutic modality.

A 47-year-old female with a history of chronic alcoholism presented with nausea, vomiting and mild epigastric tenderness. She reported subjective fever, abdominal fullness and loose, watery stools and had stable vitals on arrival. Examination was positive for mild epigastric tenderness with hepatic enlargement. Computed tomography of the abdomen showed circumferential thickening of the stomach wall, lower esophagus and the first part of the duodenum in addition to peritoneal ascites. She was admitted for alcohol-related gastritis, acute alcoholic hepatitis, and acute kidney injury. She was started on fluid resuscitation and supportive management. After 8-hours, the patient became hemodynamically unstable with subsequent intubation and fluid resuscitation. She was started on empiric antibiotics. Blood and ascitic fluid cultures were obtained showing group A beta-hemolytic streptococci (GAS). The patient was diagnosed with primary GAS peritonitis along with diffuse gastritis and streptococcal toxic shock syndrome. No cutaneous source of Streptococcus pyogenes was identified, and there was no personal or family history of streptococcal pharyngitis. Antibiotics were switched to IV ampicillin and clindamycin. However, the patient continued to deteriorate and succumbed to death within 2-days.

Takotsubo cardiomyopathy (TTC) is a syndrome characterized by transient regional systolic dysfunction of the left ventricle in the absence of angiographic evidence of obstructive coronary artery disease (CAD). A variety of stress-related triggers, including malignancies, have been reported in patients with TTC. However, to our knowledge, a recent diagnosis of a colon mass preceding the development of TTC has not been reported. We report on a female patient who was recently diagnosed with a colon mass by colonoscopy who was then scheduled to undergo robotic hemicolectomy, but was subsequently admitted to our hospital for intractable nausea and abdominal pain. While admitted, she developed transient ventricular tachycardia with elevated cardiac markers. The echocardiogram revealed markedly decreased ejection fraction and mid to distal apical akinesis with regional wall motion abnormalities. Coronary angiogram demonstrated no significant CAD, consistent with the diagnosis of TTC. The recently diagnosed colon mass was the most likely stress trigger in the development of TTC.

Introduction: Only 12% of Americans have proficient health literacy (HL). Patients hide this fact from others including physicians. This quality improvement (QI) project was developed to compare internal medicine (IM) resident physicians’ (RPs) ability to accurately predict patients with low HL and to improve IM-RPs’ understanding of low HL and its impact on patients. Aim statement: Over six-months, our aim was to increase the IM residents’ HL-knowledge by 30% as measured by an HL-Knowledge-Based-Survey. Methods: After IRB exemption, patients visiting the residency-clinic within a two-week period were screened for low HL with the REALM-R, a validated tool. Post-visit, IM-RPs were asked to predict their patients’ HL. A comparison of predicted-HL and measured-HL was made. IM-RPs were emailed an HL-Knowledge-Based-Survey (pre-education and post-education) to measure their background knowledge of HL. Education included HL-workshop, pre-clinic conference and lectures. Pre-education and post-education scores were compared. Results: HL-RPs’ prediction and patients’ REALM-R results were completed by 108 RP-patient pairs. IM-RPs correctly identified 5 of 40 patients who were at risk for low HL (sensitivity = 12.5%). They correctly identified 97.1% of 68 who were not at risk (specificity = 97.1%). Our residents’ knowledge pre-education and post-education did not improve – 58% (n = 18) vs 62% (n = 10). Conclusion: Our QI result verified that IM-RPs overestimate patients’ HL and do not understand the magnitude or consequences of low HL nor techniques to improve such patients’ understanding. This suggests an area for residency curricular development in order to improve patients’ ability to navigate the healthcare system successfully.

Primary esophageal diffuse large B-cell lymphoma (DLBCL) is an extremely rare clinicopathologic entity. We report one case from our clinical experience and undertake a review of the previously published cases. A systematic literature search of the medical databases PubMed and Google Scholar was conducted. A total of 15 cases fulfilled the inclusion criteria. The data on patients’ characteristics, epidemiology, clinical features, HIV status, gross appearance of the lesion, esophageal location, treatment, and outcome were collected and analyzed. Primary esophageal DLBCL was more common among males, primarily in the fifth and sixth decades of life. Dysphagia was the most common initial clinical presentation. Tissue biopsy with immunohistochemistry was an indispensable diagnostic modality. The mainstay of treatment was chemotherapy with cyclophosphamide, vincristine, doxorubicin, and prednisone regimen, in addition to anti-CD20 antibody rituximab, with or without radiotherapy. This review serves to outline our current understanding of the epidemiology of and risk factors for primary esophageal DLBCL, the pathophysiology of this disorder, and currently available approaches to diagnosis and management.

The dental abnormalities are the typical features of many ectodermal dysplasias along with congenital malformations of nails, skin, hair, and sweat glands. However, several reports of non-syndromic/isolated tooth agenesis have also been found in the literature. The characteristic features of hypohidrotic ectodermal dysplasia (HED) comprise of hypodontia/oligodontia, along with hypohidrosis/anhidrosis, and hypotrichosis. Pathogenic variants in EDA, EDAR, EDARADD, and TRAF6, cause the phenotypic expression of HED. Genetic alterations in EDA and WNT10A cause particularly non-syndromic/isolated oligodontia. In the current project, we recruited 57 patients of 17 genetic pedigrees (A-Q) from different geographic regions of the world, including Pakistan, Egypt, Saudi Arabia, and Syria. The molecular investigation of different syndromic and non-syndromic dental conditions, including hypodontia, oligodontia, generalized odontodysplasia, and dental crowding was carried out by using exome and Sanger sequencing. We have identified a novel missense variant (c.311G>A; p.Arg104His) in WNT10A in three oligodontia patients of family A, two novel sequence variants (c.207delinsTT, p.Gly70Trpfs*25 and c.1300T>G; p.Try434Gly) in EDAR in three patients of family B and four patients of family C, respectively. To better understand the structural and functional consequences of missense variants in WNT10A and EDAR on the stability of the proteins, we have performed extensive molecular dynamic (MD) simulations. We have also identified three previously reported pathogenic variants (c.1076T>C; p.Met359Thr), (c.1133C>T; p.Thr378Met) and (c.594_595insC; Gly201Argfs*39) in EDA in family D (four patients), E (two patients) and F (one patient), correspondingly. Presently, our data explain the genetic cause of 18 syndromic and non-syndromic tooth agenesis patients in six autosomal recessive and X-linked pedigrees (A-F), which expand the mutational spectrum of these unique clinical manifestations.